1. Field of the Invention
This invention relates to a pharmaceutical composition comprising docetaxel, methods for producing the same, and methods for using the composition.
2. Description of the Related Art
Taxanes are a class of potent anti-tumor agents. The mechanism of their action comprises binding to microtubules to promote and stabilize microtubule assembly, and further to prevent physiological microtubule depolymerisation and disassembly. This leads to a significant decrease in free tubulin, results in inhibition of mitotic cell division and apoptosis of the cancer cell.
Currently, the most widely used taxanes are paclitaxel and docetaxel, which have been approved for the treatment of primary and metastatic cancer comprising breast cancer, ovarian cancer, non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), head and neck squamous cell carcinoma, and malignant melanoma.
However, taxanes, and in particular paclitaxel and docetaxel, have very poor solubility in aqueous solutions. Thus, formulating these compounds is difficult. For example, commercially available docetaxel (Taxotere) is formulated in a highly concentrated solution containing 40 mg docetaxel and 1040 mg TWEEN® 80 (polysorbate 80) per mL. This concentrated solution has to be diluted with solvent containing 13% ethanol in saline before administration.
Although a number of methods have been reported in the literature that claim improved formulation and solubility of taxanes, these methods are based on the formation of emulsion, or microemulsion, or on the inclusion of cyclodextrins, liposomes, nanoparticles, etc. However, each of above methods is hampered by one or more problems, such as complicated preparation, high cost, and low stability of the formulations. Therefore, there is an urgent need for a pharmaceutical composition comprising taxanes, the composition having high solubility and stability, simplified preparation process, and exhibiting lower hypersensitivity in patients.